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      Is Open Access

      Cardio-Oncology : Understanding the Intersections Between Cardiac Metabolism and Cancer Biology

      review-article
      , MD, PhD a , b , ∗∗ , , BS c , , MD, MTR d , , PhD e , , MD, MSCE c , d ,
      JACC: Basic to Translational Science
      Elsevier
      cancer, cardio-oncology, heart failure, metabolism, oncometabolism, [18F]FDG, 2-deoxy-2-[fluorine-18]fluoro-D-glucose, 99mTc-MIBI, 99mtechnetium-sestamibi, α-KG, α-ketoglutarate, CVD, cardiovascular disease, D2-HG, D-2-hydroxyglutarate, FAO, fatty acid oxidation, FASN, fatty acid synthase, GLS, glutaminase, HF, heart failure, IDH, isocitrate dehydrogenase, IGF, insulin-like growth factor, MCT1, monocarboxylate transporter 1, MRS, magnetic resonance spectroscopy, PTM, post-translational modification, PI3K, insulin-activated phosphoinositide-3-kinase, PDH, pyruvate dehydrogenase, PET, positron emission tomography, SGLT2, sodium glucose co-transporter 2, TRF, time-restricted feeding

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Highlights

          • Cancer cells can promote metabolic remodeling in the heart.

          • Metabolic changes provide opportunities for novel treatment strategies to prevent heart failure and monitor disease progression through new imaging techniques.

          • Translational biomarker and imaging studies are needed to further understand the impact of cancer cell biology on the heart.

          Central Illustration

          Summary

          An important priority in the cardiovascular care of oncology patients is to reduce morbidity and mortality, and improve the quality of life in cancer survivors through cross-disciplinary efforts. The rate of survival in cancer patients has improved dramatically over the past decades. Nonetheless, survivors may be more likely to die from cardiovascular disease in the long term, secondary, not only to the potential toxicity of cancer therapeutics, but also to the biology of cancer. In this context, efforts from basic and translational studies are crucial to understanding the molecular mechanisms causal to cardiovascular disease in cancer patients and survivors, and identifying new therapeutic targets that may prevent and treat both diseases. This review aims to highlight our current understanding of the metabolic interaction between cancer and the heart, including potential therapeutic targets. An overview of imaging techniques that can support both research studies and clinical management is also provided. Finally, this review highlights opportunities and challenges that are necessary to advance our understanding of metabolism in the context of cardio-oncology.

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          Most cited references173

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Understanding the Warburg effect: the metabolic requirements of cell proliferation.

            In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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              On the origin of cancer cells.

              O WARBURG (1956)
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                Author and article information

                Contributors
                Journal
                JACC Basic Transl Sci
                JACC Basic Transl Sci
                JACC: Basic to Translational Science
                Elsevier
                2452-302X
                28 July 2021
                August 2021
                28 July 2021
                : 6
                : 8
                : 705-718
                Affiliations
                [a ]Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
                [b ]Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
                [c ]Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
                [d ]Departments of Medicine and Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
                [e ]Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
                Author notes
                [] Address for correspondence: Dr Bonnie Ky, Perelman Center for Advanced Medicine, University of Pennsylvania, East Pavilion, 2nd Floor, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA. Bonnie.Ky@ 123456pennmedicine.upenn.edu
                [∗∗ ]Dr Anja Karlstaedt, Department of Cardiology, Smidt Heart Institute, 127 South San Vincente Boulevard, AHSP 9229, Los Angeles, California 90048, USA. anja.karlstaedt@ 123456csmc.edu
                Article
                S2452-302X(21)00203-5
                10.1016/j.jacbts.2021.05.008
                8385559
                34466757
                7f80c695-a54e-4f35-9987-5d3bf0f36977
                © 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 March 2021
                : 21 May 2021
                : 23 May 2021
                Categories
                State-of-the-Art Review

                cancer,cardio-oncology,heart failure,metabolism,oncometabolism,[18f]fdg, 2-deoxy-2-[fluorine-18]fluoro-d-glucose,99mtc-mibi, 99mtechnetium-sestamibi,α-kg, α-ketoglutarate,cvd, cardiovascular disease,d2-hg, d-2-hydroxyglutarate,fao, fatty acid oxidation,fasn, fatty acid synthase,gls, glutaminase,hf, heart failure,idh, isocitrate dehydrogenase,igf, insulin-like growth factor,mct1, monocarboxylate transporter 1,mrs, magnetic resonance spectroscopy,ptm, post-translational modification,pi3k, insulin-activated phosphoinositide-3-kinase,pdh, pyruvate dehydrogenase,pet, positron emission tomography,sglt2, sodium glucose co-transporter 2,trf, time-restricted feeding

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